Gastrointestinal diseases continue to be significant public health problems on a worldwide scale. Acute and persistent diarrheal diseases claim nearly one million lives of children under age 5 each year. In addition, repeated episodes of diarrhea lead to malnutrition, stunting, lower neurodevelopment scores, and may increase the risk of some chronic diseases. Although improvements in the composition of oral rehydration solutions have reduced the burden of diarrhea, millions of children die of diarrheal diseases and associated complications each year. In industrialized countries, children with intestinal failure (short bowel syndrome and other disorders) suffer from chronic diarrhea and malnutrition requiring treatment with specialized parenteral and enteral nutrition. With the renewal of this mid-career investigator award, Christopher Duggan, MD, MPH seeks to continue to expand his mentorship of young investigators and extend his research in improving clinical outcomes for children with diarrheal diseases. Dr. Duggan will expand his research in the areas of intestinal failure and diarrheal diseases, collaborating with experts in mucosal immunity and developmental origins of health and disease. During the initial grant period, he performed a number of important studies in the fields of diarrheal disease treatment and prevention, and has mentored numerous young colleagues. He leads important research efforts to derive and validate new biomarkers of gastrointestinal function in Tanzanian children who participated in his R01- funded micronutrient clinical trial, and now proposes to evaluate these biomarkers in US children with intestinal failure. He is a faculty member of several well-established T32 training grants that will allow him to mentor physician scientists and graduate students of outstanding promise in the fields of pediatric gastroenterology, nutrition, GI surgery, global health and outcomes research. He will continue to foster the skills and clinical research infrastructure to enable younger investigators to develop along productive career trajectories.